The primary purpose of this study is to assess the safety and tolerability of lunresertib alone and in combination with RP-3500 or in combination with Debio 0123 in patients with eligible advanced solid tumors, determine the maximum tolerated dose (MTD) and assess preliminary anti-tumor activity.
Phase 1/1b, multi-center, open-label, dose-escalation study to: * Evaluate the safety profile and MTD of lunresertib alone and in combination with RP-3500 or in combination with Debio 0123 when administered orally to establish the recommended Phase 2 dose and schedule * Characterize the PK and pharmacodynamics of lunresertib alone and in combination with RP-3500 or in combination with Debio 0123 * Assess preliminary anti-tumor activity associated with lunresertib alone and in combination with RP-3500 or in combination with Debio 0123 This study was previously posted by Repare Therapeutics. In September 2025, sponsorship of the trial was transferred to Debiopharm International S.A Expanded Access Status: There is no expanded access program available for the investigational products in this study at this time.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
464
Safety and Tolerability of lunresertib either in monotherapy or in combination with RP-3500 or with Debio 0123 in patients with eligible advanced solid tumors
Assessed by treatment-emergent adverse events (TEAEs), physical examinations (PEs), safety laboratory assessments, electrocardiograms (ECGs), and vital sign measurements
Time frame: Up to 90 days after last administration of study intervention
To define the MTD of lunresertib monotherapy, and determine a recommended Phase 2 dose (RP2D) and preferred schedule
Assessed by the incidence of Dose-limiting toxicities (DLTs) and the incidence and severity of cumulative safety data
Time frame: Up to 90 days after last administration of study intervention
To define the MTD of lunresertib in combination with RP-3500 or in combination with Debio 0123, and determine a recommended Phase 2 dose (RP2D) and preferred schedule
Assessed by the incidence of dose-limiting toxicities (DLTs) and the incidence and severity of cumulative safety data
Time frame: Up to 90 days after last administration of study intervention
The relative bioavailability of lunresertib capsule formulation as compared to lunresertib tablet formulation in the fasted state
Assessed by the plasma concentrations of lunresertib with calculation of pharmacokinetic (PK) parameters including maximum observed plasma concentration (Cmax), time to maximum observed plasma concentration (Tmax), area under the plasma concentration-time curve (AUC) , for both formulations in the fasted state.
Time frame: Time 0 (time of dosing) to 72 hours post-dose for each treatment condition
The effect of food on the PK of tablet formulation of lunresertib when administered in fed conditions compared to administration under fasted conditions
Assessed by the plasma concentrations of lunresertib with calculation of the ratio of PK parameters (e.g., Cmax and AUC) between the tablet formulation under fasted and fed state.
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# 1019, UCLA, Westwood Cancer Center
Los Angeles, California, United States
COMPLETED#1025, University of California San Francisco
San Francisco, California, United States
RECRUITING#1012, Yale
New Haven, Connecticut, United States
RECRUITING#1017, Mayo Clinic
Jacksonville, Florida, United States
RECRUITING#1002, Dana Farber Cancer Institute
Boston, Massachusetts, United States
RECRUITING#1023, START Midwest
Grand Rapids, Michigan, United States
RECRUITING#1016, Mayo Clinic
Rochester, Minnesota, United States
RECRUITING#1011, Washington University
St Louis, Missouri, United States
RECRUITING#1032, Northwell Health Cancer Institute
New Hyde Park, New York, United States
RECRUITING#1008, Columbia University
New York, New York, United States
COMPLETED...and 16 more locations
Time frame: Time 0 (time of dosing) to 72 hours post-dose for each treatment condition
To assess the safety and tolerability of lunresertib tablets in combination with RP-3500, confirm the MTD of lunresertib tablets in combination with RP-3500, and determine a RP2D and preferred schedule
Assessed by DLTs, TEAEs, safety laboratory assessments, the incidence of DLTs and the incidence and severity of cumulative safety data
Time frame: Up to 90 days after last administration of study intervention
The plasma concentrations of lunresertib monotherapy (capsule formulation) in the fasted and fed states
Assessed by the plasma concentrations of lunresertib with calculation of maximum observed plasma concentration (Cmax), time to maximum observed plasma concentration (Tmax), minimum observed plasma concentration (Cmin), area under the plasma concentration-time curve (AUC), elimination half-life (t1/2), and other parameters as appropriate
Time frame: Up to 90 days after last administration of study intervention
To assess the relationship between pharmacodynamic biomarkers and PK of lunresertib at different dose levels and/or schedules
Assessed by evaluation of biomarkers in pre- and on-treatment biopsies, and circulating tumor DNA (ctDNA) dynamics during treatment
Time frame: Up to 90 days after last administration of study intervention
The plasma concentrations of lunresertib and RP-3500 when dosed in combination
Assessed by the plasma concentrations of lunresertib and RP-3500 with calculation of maximum observed plasma concentration (Cmax), time to maximum observed plasma concentration (Tmax), minimum observed plasma concentration (Cmin), area under the plasma concentration-time curve (AUC), elimination half-life (t1/2), and other parameters as appropriate for each analyte
Time frame: Up to 90 days after last administration of study intervention
To assess preliminary anti-tumor activity achieved with lunresertib monotherapy, lunresertib in combination with RP-3500 or lunresertib in combination with Debio 0123
Measured by best percent change in tumor size from baseline, objective response rate (ORR), overall response rate, tumor marker response, duration of response (DOR), clinical benefit rate (CBR), progression-free survival (PFS).
Time frame: Through Study Completion, an average of 1 year
To assess the safety and anti-tumor effects of lunresertib capsule + RP-3500
As measure by TEAEs, safety laboratory assessments, Best percent change in tumor size from baseline, ORR, overall response rate, DOR, CBR, tumor marker response, PFS
Time frame: Through Study Completion, an average of 1 year
To further characterize the PK of lunresertib tablets and assess preliminary anti-tumor
Measured by Plasma concentrations of lunresertib with calculation of Cmax, Tmax, AUC, elimination t1/2, and other PK parameters as appropriate, Best percent change in tumor size from baseline, ORR, overall response rate, DOR, CBR, tumor marker response, PFS
Time frame: Through Study Completion, an average of 1 year